SEMANTIC HYPERCAT

The rapidly increasing number of sensor networks and smart devices contributed to the generation of a huge number of information. Information that is generated by several sources and is available indifferent formats highlights interoperability as one of the key preconditions for the success of the Internet of Things (IoT). Hypercat is a specification defining a JSON-based catalogue, designed to serve the needs of the industry. In this thesis, I extend the existing work on semantic enrichment of Hypercat by defining a JSON-LD based catalogue. The proposed JSON-LD specification offers a mapping mechanism among JSON and JSON-LD catalogues, while highlighting the fact that JSON-LD could be seamlessly adopted by the Hypercat community

RPGR-Related Retinopathy: Clinical Features, Molecular Genetics, and Gene Replacement Therapy

Retinitis pigmentosa GTPase regulator (RPGR) gene variants are the predominant cause of X-linked retinitis pigmentosa (XLRP) and a common cause of cone-rod dystrophy (CORD). XLRP presents as early as the first decade of life, with impaired night vision and constriction of peripheral visual field and rapid progression, eventually leading to blindness. In this review, we present RPGR gene structure and function, molecular genetics, animal models, RPGR-associated phenotypes and highlight emerging potential treatments such as gene-replacement therapy

Multimorbidity due to novel pathogenic variants in the WFS1/RP1/NOD2 genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family

Background: A five generation family has been analysed by whole exome sequencing (WES) for genetic associations with the multimorbidities of congenital cataract (CC), retinitis pigmentosa (RP) and Crohn’s disease (CD). // Methods: WES was performed for unaffected and affected individuals within the family pedigree followed by bioinformatic analyses of these data to identify disease-causing variants with damaging pathogenicity scores. // Results: A novel pathogenic missense variant in WFS1: c.1897G>C; p.V633L, a novel pathogenic nonsense variant in RP1: c.6344T>G; p.L2115* and a predicted pathogenic missense variant in NOD2: c.2104C>T; p.R702W are reported. The three variants cosegregated with the phenotypic combinations of autosomal dominant CC, RP and CD within individual family members. // Conclusions: Here, we report multimorbidity in a family pedigree listed on a CC register, which broadens the spectrum of potential cataract associated genes to include both RP1 and NOD2

Inherited causes of combined vision and hearing loss: clinical features and molecular genetics

Combined vision and hearing loss, also known as dual sensory impairment, can occur in several genetic conditions, including ciliopathies such as Usher and Bardet-Biedl syndrome, mitochondrial DNA disorders and systemic diseases, such as CHARGE, Stickler, Waardenburg, Alport and Alstrom syndrome. The retinal phenotype may point to the diagnosis of such disorders. Herein, we aim to provide a comprehensive review of the molecular genetics and clinical features of the most common non-chromosomal inherited disorders to cause dual sensory impairment

The evolution of labour law in the new member states of the European Union : 1995-2005 - country studies on Cyprus and Malta

This Report traces the development of Labour Law and the implications for Industrial Relations, as well as social and employment policy more generally, in the two small Mediterranean countries of Cyprus and Malta during the period 1995–2005. This period was particularly important for the two countries as it coincided with their efforts for accession to the European Union (EU) and the process of harmonisation with the Acquis Communautaire. Since their independence in 1960 and 1964 respectively for Cyprus and Malta, successive Governments in each country – working with the social partners – had sought to steer a policy of social cohesion to underpin their development efforts. Whilst these strategies were successful in fostering a long period of economic growth and peaceful labour relations, a major outcome was the existence of relatively inflexible labour markets. Liberalisation and globalisation of international markets, coupled with the pressure exerted by the accession process, which required the implementation of the Acquis Communautaire necessitated a series of changes with far reaching implications in social and economic affairs. Naturally the framework of Labour Law – and labour practices thereof – came under increasing pressure to adapt and reform. The Executive Summary describes the main aims and objectives of the Report on the evolution of Labour Law in Cyprus and Malta in the period 1995-2005, and provides an outline of the component chapters. Specifically the Report is divided into three chapters. The first and second chapters consist of the individual Reports on Cyprus and Malta respectively. These constitute the main body of the Report and investigate the evolution of Labour Law in the two countries separately and the implications for Industrial Relations, employment and social policy. The third chapter provides a concluding overview of the two countries’ experiences and an evaluation of the state of implementation of the Acquis Communautaire in the fields examined.peer-reviewe

The genetic landscape of crystallins in congenital cataract

Background: The crystalline lens is mainly composed of a large family of soluble proteins called the crystallins, which are responsible for its development, growth, transparency and refractive index. Disease-causing sequence variants in the crystallins are responsible for nearly 50% of all non-syndromic inherited congenital cataracts, as well as causing cataract associated with other diseases, including myopathies. To date, more than 300 crystallin sequence variants causing cataract have been identified. Methods: Here we aimed to identify the genetic basis of disease in five multi-generation British families and five sporadic cases with autosomal dominant congenital cataract using whole exome sequencing, with identified variants validated using Sanger sequencing. Following bioinformatics analysis, rare or novel variants with a moderate to damaging pathogenicity score, were filtered out and tested for segregation within the families. Results: We have identified 10 different heterozygous crystallin variants. Five recurrent variants were found: family-A, with a missense variant (c.145C>T; p.R49C) in CRYAA associated with nuclear cataract; family-B, with a deletion in CRYBA1 (c.272delGAG; p.G91del) associated with nuclear cataract; and family-C, with a truncating variant in CRYGD (c.470G>A; W157*) causing a lamellar phenotype; individuals I and J had variants in CRYGC (c.13A>C; T5P) and in CRYGD (c.418C>T; R140*) causing unspecified congenital cataract and nuclear cataract, respectively. Five novel disease-causing variants were also identified: family D harboured a variant in CRYGC (c.179delG; R60Qfs*) responsible for a nuclear phenotype; family E, harboured a variant in CRYBB1 (c.656G>A; W219*) associated with lamellar cataract; individual F had a variant in CRYGD (c.392G>A; W131*) associated with nuclear cataract; and individuals G and H had variants in CRYAA (c.454delGCC; A152del) and in CRYBB1 (c.618C>A; Y206*) respectively, associated with unspecified congenital cataract. All novel variants were predicted to be pathogenic and to be moderately or highly damaging. Conclusions: We report five novel variants and five known variants. Some are rare variants that have been reported previously in small ethnic groups but here we extend this to the wider population and record a broader phenotypic spectrum for these variants

Characterization of Retinal Structure in ATF6-Associated Achromatopsia.

PurposeMutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM.MethodsSeven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM.ResultsFoveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports.ConclusionsOur data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM